Differences in structural and functional default mode network connectivity in amyloid positive mild cognitive impairment: a longitudinal study

Purpose Default mode network (DMN) has emerged as a potential biomarker of Alzheimer's disease (AD); however, it is not clear whether it can differentiate amnestic mild cognitive impairment with altered amyloid (aMCI-A beta +) who will evolve to AD. We evaluated if structural and functional connectivity (FC), hippocampal volumes (HV), and cerebrospinal fluid biomarkers (CSF-A beta(42), p-Tau, and t-Tau) can differentiate aMCI-A beta + converters from non-converters. Methods Forty-eight individuals (18 normal controls and 30 aMCI subjects in the AD continuum - with altered A beta(42) in the CSF) were followed up for an average of 13 months. We used MultiAtlas, (UFC)-C-2, and Freesurfer software to evaluate diffusion tensor imaging, FC, and HV, respectively, INNOTEST (R) kits to measure CSF proteins, and neuropsychological tests. Besides, we performed different MANOVAs with further univariate analyses to differentiate groups. Results During follow-up, 8/30 aMCI-A beta + converted (26.6%) to AD dementia. There were no differences in multivariate analysis between groups in CSF biomarkers (p = 0.092) or at DMN functional connectivity (p = 0.814). aMCI-A beta + converters had smaller right HV than controls (p = 0.013), and greater right cingulum parahippocampal bundle radial diffusivity than controls (p < 0.001) and non-converters (p = 0.036). Conclusion In this exploratory study, structural, but not functional, DMN connectivity alterations may differentiate aMCI-A beta + subjects who converted to AD dementia.

Automated summary

This study found that structural connectivity alterations, but not functional connectivity changes, may differentiate individuals with amnestic mild cognitive impairment with altered amyloid who will evolve to Alzheimer's disease dementia.